Use of micro-computed tomography to evaluate changes to bone structure due to ovariectomy and polyunsaturated fatty acid intervention in a rat model of postmenopausal osteoporosis
The testing of osteoporosis-related therapies and the investigation into their mechanism of action largely relies on the use of the preclinical model of postmenopausal osteoporosis, the ovariectomized (OVX) rat. Study 1 evaluated the time-course of changes to the trabecular and cortical microarchitecture of the proximal tibia of the Sham-control and OVX rat over a 3-month period following surgery at 3-months of age, a typical period used in the testing of nutritional and/or drug intervention. This study confirmed the use of the 3-month OVX rat as a model for trabecular microarchitecture changes, but did not support its use as a model for cortical bone changes. The OVX rat was also used to test its resistance to repeated radiation exposure from micro-computed tomography (μCT), a method necessary for the longitudinal evaluation of a single animal (Study 2). The method of μCT and its scanning parameters were also investigated to confirm their use in appropriately quantifying the 3-dimensional microarchitecture of the rat hind limb both in vivo and ex vivo (Study 3). Together, findings from these methodological studies led to its use in the evaluation of changes to bone structure in response to a nutritional intervention in the OVX rat (Study 4). Previous studies of growing rats and of OVX rats suggest a benefit to bone with supplementation with a lower n-6 to n-3 polyunsaturated fatty acid (PUFA) dietary ratio, and to altered sources of n-3 PUFA, but no study has investigated the impact of these nutritional patterns over the life course. Therefore, Study 4 determined the effect of the dietary ratio and source of n- 3 PUFA on bone during periods of growth (1 through 3 months of age) and following Sham or OVX surgery (at 3 months of age). A low PUFA ratio with n-3 provided from flaxseed oil provided benefits to bone health during growth, but these changes were not maintained following OVX. These data suggest that dietary PUFA, at levels attainable in humans through a healthful diet, are not an adequate strategy for the prevention of the rapid and drastic bone loss induced by OVX.